Complexing a DNA primer with an RNA template showed improved nonenzymatic template-directed primer extension, attributed to a shift in the DNA helicity from a B-type towards an A-type helix. A 2-fold (deoxyadenosine) and 4.5-fold (deoxycytidine) increase in conversion from initial DNA primer to a primer + 1 nucleotide product was observed.
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http://dx.doi.org/10.1039/d3ob01179h | DOI Listing |
Nucleic Acids Res
December 2024
Department of Chemistry, 5735 South Ellis Avenue, The University of Chicago, Chicago, IL 60637, USA.
The RNA World hypothesis posits that RNA was the molecule of both heredity and function during the emergence of life. This hypothesis implies that RNA templates can be copied, and ultimately replicated, without the catalytic aid of evolved enzymes. A major problem with nonenzymatic template-directed polymerization has been the very poor copying of sequences containing rA and rU.
View Article and Find Full Text PDFLife (Basel)
August 2024
Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, São Carlos 13560-970, SP, Brazil.
The population dynamics of early replicators has revealed numerous puzzles, highlighting the difficulty of transitioning from simple template-directed replicating molecules to complex biological systems. The resolution of these puzzles has set the research agenda on prebiotic evolution since the seminal works of Manfred Eigen in the 1970s. Here, we study the effects of demographic noise on the population dynamics of template-directed (non-enzymatic) and protein-mediated (enzymatic) replicators.
View Article and Find Full Text PDFJ Am Chem Soc
April 2024
Department of Chemistry, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, United States.
Nonenzymatic template-directed RNA copying requires catalysis by divalent metal ions. The primer extension reaction involves the attack of the primer 3'-hydroxyl on the adjacent phosphate of a 5'-5'-imidazolium-bridged dinucleotide substrate. However, the nature of the interaction of the catalytic metal ion with the reaction center remains unclear.
View Article and Find Full Text PDFChembiochem
April 2024
Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Non-enzymatic template-directed primer extension is increasingly being studied for the production of RNA and DNA. These reactions benefit from producing RNA or DNA in an aqueous, protecting group free system, without the need for expensive enzymes. However, these primer extension reactions suffer from a lack of fidelity, low reaction rates, low overall yields, and short primer extension lengths.
View Article and Find Full Text PDFFEBS Lett
December 2023
Department of Biology, Indian Institute of Science Education and Research, Pune, Maharashtra, India.
Nonenzymatic template-directed replication would have been affected by co-solutes in a heterogeneous prebiotic soup due to lack of enzymatic machinery. Unlike in contemporary biology, these reactions use chemically activated nucleotides, which undergo rapid hydrolysis forming nucleoside monophosphates ('spent' monomers). These co-solutes cannot extend the primer but continue to base pair with the template, thereby interfering with replication.
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